{(S)-2-{3-Methyl-4-[(R)-1,1,3-trioxo-2-(2-trimethylsilanyl-ethoxymethyl)-1λ⁶-isothiazolidin-5-yl]-phenyl}-1-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-ethyl}-carbamic acid benzyl ester | 850321-36-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {(S)-2-{3-Methyl-4-[(R)-1,1,3-trioxo-2-(2-trimethylsilanyl-ethoxymethyl)-1λ⁶-isothiazolidin-5-yl]-phenyl}-1-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-ethyl}-carbamic acid benzyl ester
• 英文别名: benzyl N-[(1S)-2-[3-methyl-4-[(5R)-1,1,3-trioxo-2-(2-trimethylsilylethoxymethyl)-1,2-thiazolidin-5-yl]phenyl]-1-[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]ethyl]carbamate
• CAS: 850321-36-7
• 化学式: C₃₉H₅₄N₄O₇SSi₂
• 分子量: 779.117
• InChiKey: NQCNUQCIEFDXTD-PUDHBBIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.78
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  {(S)-2-{3-Methyl-4-[(R)-1,1,3-trioxo-2-(2-trimethylsilanyl-ethoxymethyl)-1λ⁶-isothiazolidin-5-yl]-phenyl}-1-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-ethyl}-carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-{(S)-2-{3-Methyl-4-[(R)-1,1,3-trioxo-2-(2-trimethylsilanyl-ethoxymethyl)-1λ⁶-isothiazolidin-5-yl]-phenyl}-1-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-ethyl}-benzenesulfonamide
  参考文献：
  名称：

  Potent Benzimidazole Sulfonamide Protein Tyrosine Phosphatase 1B Inhibitors Containing the Heterocyclic (S)-Isothiazolidinone Phosphotyrosine Mimetic

  摘要：

  Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine ( pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 angstrom resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole. The ortho substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme inhibitors of PTP1B that also displayed low caco-2 permeability and cellular activity in an insulin receptor (IR) phosphorylation assay and an Akt phosphorylation assay. The design, synthesis, and SAR of this novel series of benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented herein.

  DOI：

  10.1021/jm0600904
• 作为产物：
  描述：

  benzyl (1S)-2-[(2-aminophenyl)amino]-1-[4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-methylbenzyl]-2-oxoethylcarbamate trifluoroacetate 在 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 {(S)-2-{3-Methyl-4-[(R)-1,1,3-trioxo-2-(2-trimethylsilanyl-ethoxymethyl)-1λ⁶-isothiazolidin-5-yl]-phenyl}-1-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-ethyl}-carbamic acid benzyl ester
  参考文献：
  名称：

  Potent Benzimidazole Sulfonamide Protein Tyrosine Phosphatase 1B Inhibitors Containing the Heterocyclic (S)-Isothiazolidinone Phosphotyrosine Mimetic

  摘要：

  Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine ( pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 angstrom resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole. The ortho substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme inhibitors of PTP1B that also displayed low caco-2 permeability and cellular activity in an insulin receptor (IR) phosphorylation assay and an Akt phosphorylation assay. The design, synthesis, and SAR of this novel series of benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented herein.

  DOI：

  10.1021/jm0600904